Human adenoviruses have well documented oncogenic potential in experimental animals and in vitro. Adenoviruses are not viewed as candidates for a major etiological role in human malignancy but they serve as a convenient probe in tumor biology. The transforming capacity of adenoviruses is associated with the left hand end of their genome which codes for transformation proteins. The products of this region of adenovirus type 12 genome will be isolated and characterized. We will attempt to define the mechanisms by which these products establish oncogenic transformation. Although all adenoviruses can transform cells in vitro, in vivo oncogenic potential of different serotypes varies from highly oncogenic to nononcogenic. The adenovirus-specific surface antigens will be identified in transformed cells and their role in the induction of the immune response will be analyzed. The immune response to cells transformed with highly oncogenic and nononcogenic adenoviruses will be qualitatively and quantitatively compared in syngeneic hosts. Data will be obtained indicating whether the immune response plays a major role in differences in tumorigenicity of individual adenoviruses in vivo.